In May 2009, the band embarked on a concert tour in support of the album — called Tour of the Universe; it had been announced at a press conference in October 2008 at the Olympiastadion in Berlin. There was a warm up show in Luxembourg and it officially started on 10 May 2009 in Tel Aviv. The first leg of the tour was disrupted when Dave Gahan was struck down with gastroenteritis. During treatment, doctors found and removed a low grade tumour from the singer's bladder. Gahan's illness caused 16 concerts to be cancelled, but several of the shows were rescheduled for 2010. The band headlined the Lollapalooza festival during the North American leg of the tour. The tour also took the band back to South America for the first time since 1994's Exotic Tour. During the final European leg, the band played a show at London's Royal Albert Hall in aid of the Teenage Cancer Trust, where former member Alan Wilder joined Martin Gore on stage for a performance of "Somebody". In total the band played to more than 2.7 million people across 32 countries and the tour was one of the most profitable in America in 2009. The concerts held at Palau Sant Jordi, Barcelona, Spain were filmed and later released on DVD and Blu-ray Disc release entitled Tour of the Universe: Barcelona 20/21.11.09. In March 2010, Depeche Mode won the award for "Best International Group – Rock / Pop" at the ECHO Awards in Germany.

Depeche Mode's origins date to 1977, when schoolmates Vince Clarke and Andy Fletcher formed a Cure-influenced band called No Romance In China, with Clarke on vocals and guitar and Fletcher on bass guitar. Fletcher would later recall, "Why am I in the band? It was accidental right from the beginning. I was actually forced to be in the band. I played the guitar and I had a bass; it was a question of them roping me in." In 1979, Clarke played guitar in an "Ultravox rip-off band", The Plan, with friends Robert Marlow and Paul Langwith. In 1978–79, Martin Gore played guitar in an acoustic duo, Norman and the Worms, with school friend Phil Burdett on vocals. In 1979, Marlow, Gore and friend Paul Redmond formed a band called the French Look, with Marlow on vocals/keyboards, Gore on guitar and Redmond on keyboards. In March 1980, Clarke, Gore and Fletcher formed a band called Composition of Sound, with Clarke on vocals/guitar, Gore on keyboards and Fletcher on bass.

Dave Gahan's heroin addiction was increasingly affecting his behaviour, causing him to become more erratic and introverted. Martin Gore experienced seizures, and Andy Fletcher declined to participate in the second half of the Exotic Tour due to "mental instability". During that period, he was replaced on stage by Daryl Bamonte, who had worked with the band as a personal assistant, since the beginning of their career in 1980.

In late 1981, the band placed an anonymous ad in Melody Maker looking for another musician: "Name band, synthesise, must be under twenty-one." Alan Wilder, a classically trained keyboardist from West London, responded and, after two auditions and despite being 22 years old, was hired in early 1982, initially on a trial basis as a touring member. Wilder would later be called the "Musical Director" of the band, responsible for the band's sound until his departure in 1995. As Producer Flood would say, "[Alan] is sort of the craftsman, Martin's the idea man and [Dave] is the attitude."

In January 1982, the band released "See You", their first single without Clarke, which managed to beat all three Clarke-penned singles in the UK charts, reaching number six. The following tour saw the band playing their first shows in North America. Two more singles, "The Meaning of Love" and "Leave in Silence," were released ahead of the band's second studio album, on which they began work in July 1982. Daniel Miller informed Wilder that he was not needed for the recording of the album, as the core trio wanted to prove they could succeed without Vince Clarke. A Broken Frame was released that September, and the following month the band began their 1982 tour. A non-album single, "Get the Balance Right!," was released in January 1983, the first Depeche Mode track to be recorded with Wilder.

"Everything Counts" rose to number six in the UK, also reaching the top 30 in Ireland, South Africa, Switzerland, Sweden and West Germany. Wilder contributed two songs to the album, "The Landscape Is Changing" and "Two Minute Warning". In September 1983, to promote Construction Time Again, the band launched a European concert tour.

The World We Live In and Live in Hamburg was the band's first video release, almost an entire concert from their 1984 Some Great Reward Tour. In July 1985, the band played their first-ever concerts behind the Iron Curtain, in Budapest and Warsaw. In October 1985, Mute released a compilation, The Singles 81→85 (Catching Up with Depeche Mode in the US), which included the two non-album hit singles "Shake the Disease" and "It's Called a Heart".

Depeche Mode's musical style shifted slightly again in 1986 with the release of their fifteenth single, "Stripped", and its accompanying album Black Celebration. Retaining their often imaginative sampling and beginning to move away from the "industrial pop" sound that had characterised their previous two LPs, the band introduced an ominous, highly atmospheric and textured sound. Gore's lyrics also took on a darker tone and became even more pessimistic.

The Music for the Masses Tour began 22 October 1987. On 7 March 1988, with no previous announcement that they would be the headlining act, Depeche Mode played in the Werner-Seelenbinder-Halle, East Berlin, becoming one of the few Western groups to perform in the Communist East Germany. They also performed concerts in Budapest and Prague in 1988, both at the time also Communist.

The world tour ended 18 June 1988 with a concert at the Pasadena Rose Bowl with paid attendance of 60,453, the highest in eight years for the venue. The tour was a breakthrough for the band and a massive success in the United States. It was documented in 101 – a concert film by D. A. Pennebaker and its accompanying Soundtrack album. The film is notable for its portrayal of fan interaction. Alan Wilder is credited with coming up with the title, noting that the performance was the 101st and final performance of the tour. On 7 September 1988, Depeche Mode performed "Strangelove" at the 1988 MTV Video Music Awards at the Universal Amphitheatre in Los Angeles.

In mid-1989, the band began recording in Milan with Producer Flood and Engineer François Kevorkian. The initial result of this session was the single "Personal Jesus." Prior to its release, a marketing campaign was launched with advertisements placed in the personals columns of UK regional newspapers with the words "Your own personal Jesus." Later, the ads included a phone number one could dial to hear the song. The resulting furor helped propel the single to number 13 on the UK charts, becoming one of their biggest sellers to date; in the United States, it was their first gold single and their first Top 40 hit since "People Are People," eventually becoming the biggest-selling 12-inch single in Warner Records' history up to that point.

Released in January 1990, "Enjoy the Silence" reached number six in the UK (the first Top 10 hit in that country since "Master And Servant"). A few months later in the US, it reached number eight and earned the band a second gold single. It won "Best British single" at the 1991 Brit Awards. To promote their new album, Violator, the band held an in-store autograph signing at Wherehouse Entertainment in Los Angeles. The event attracted approximately 20,000 fans and turned into a near riot. Some who attended were injured by being pressed against the store's glass by the crowd. As an apology to the fans who were injured, the band released a limited edition cassette tape to fans living in Los Angeles, distributed through radio station KROQ (the sponsor of the Wherehouse event).

Depeche Mode contributed their cover of the U2 song "So Cruel" to the tribute album AHK-toong BAY-bi Covered honouring the 20th anniversary of Achtung Baby, a 1991 album by U2. The compilation CD was released with the December 2011 issue of Q Magazine.

The members of Depeche Mode regrouped in Madrid in January 1992, Dave Gahan had become interested in the new grunge scene sweeping the U.S. and was influenced by the likes of Jane's Addiction, Soundgarden and Nirvana.

In 1993, Songs of Faith and Devotion, again with Flood producing, saw them experimenting with arrangements based as much on heavily distorted electric guitars and live drums (played by Alan Wilder, whose debut as a studio Drummer had come on the Violator track "Clean") as on synthesizers. Live strings, uilleann pipes and female gospel vocals were other new additions to the band's sound. The album debuted at number one in both the UK and the US, only the sixth British act to achieve such a distinction to date. The first single from the album was the grunge-influenced "I Feel You". The gospel influences are most noticeable on the album's third single, "Condemnation". A symptom of the slow fracturing of the band, interviews given by the band during this period tended to be conducted separately, unlike earlier albums, where the band was interviewed as a group.

The tour continued into 1994 with the Exotic Tour, which began in February 1994 in South Africa, and ended in April in Mexico. The final leg of the tour, consisting of more North American dates, followed shortly thereafter and ran until July. As a whole, the Devotional Tour is to date the longest and most geographically diverse Depeche Mode tour, spanning fourteen months and 159 individual performances. Q magazine described the 1993 Devotional Tour as "The Most Debauched Rock'n'Roll Tour Ever".

Despite Gahan's increasingly severe personal problems, Gore tried repeatedly during 1995 and 1996 to get the band recording again. However, Gahan would rarely turn up to scheduled sessions, and when he did, it would take weeks to get any vocals recorded; one six-week session at Electric Lady in New York produced just one usable vocal (for "Sister of Night"), and even that was pieced together from multiple takes. Gore was forced to contemplate breaking the band up and considered releasing the songs he had written as a solo album. In mid-1996, after his near-fatal overdose, Gahan entered a court-ordered drug rehabilitation program to battle his addiction to cocaine and heroin. With Gahan out of rehab in 1996, Depeche Mode held recording sessions with Producer Tim Simenon.

Preceded by two singles, "Barrel of a Gun" and "It's No Good," the album Ultra was released in April 1997. The album debuted at No. 1 in the UK (as well as Germany), and No. 5 in the US. The band did not tour in support of the album, with Fletcher quoted as saying

In March 2001, Depeche Mode held a press conference at the Valentino Hotel in Hamburg to announce the Exciter Tour. The tour featured 84 performances for over 1.5 million fans in 24 countries. The concerts held in Paris at the Palais Omnisports de Paris-Bercy were filmed and later released in May 2002 as a live DVD entitled One Night in Paris.

In October 2002 the band won the first-ever Q magazine "Innovation Award".

In 2003, Gahan released his first solo album, Paper Monsters, and toured to promote the record. Also released in 2003 was Gore's second solo album Counterfeit². Fletcher founded his own record label, Toast Hawaii, specialising in promoting electronic music.

To promote Playing the Angel, the band launched Touring the Angel, a concert tour of Europe and North America that began in November 2005 and ran for nine months. During the last two legs of the tour Depeche Mode headlined a number of festivals including the Coachella Valley Music and Arts Festival and the O₂ Wireless Festival. In total, the band played to more than 2.8 million people across 31 countries and the tour was one of the highest grossing and critically acclaimed tours of 2005/06. Speaking about the tour, Gahan praised it as "probably the most enjoyable, rewarding live shows we've ever done. The new material was just waiting to be played live. It took on a life of its own. With the Energy of the crowds, it just came to life." Two shows at Milan's Fila Forum were filmed and edited into a concert film, released on DVD as Touring the Angel: Live in Milan.

In December 2006, iTunes released The Complete Depeche Mode as its fourth ever digital box-set.

In August 2007, during promotion for Dave Gahan's second solo album, Hourglass, it was announced that Depeche Mode were heading back in studio in early 2008 to work on a new album.

In May 2008, the band returned to the studio with Producer Ben Hillier to work on some songs that Martin Gore had demoed at his home studio in Santa Barbara, California. Later that year it was announced that Depeche Mode were splitting from their long-term US label, Warner Music, and signing with EMI Music worldwide. The album was created in four sessions, two in New York and two in Santa Barbara. A total of 22 songs were recorded, with the standard album being 13 songs in length while many of the others were released in subsequent deluxe editions.

On 23 April 2009, Depeche Mode performed for the television program Jimmy Kimmel Live! at the famed corner of Hollywood Boulevard and Vine Street, drawing more than 12,000 fans, which was the largest audience the program had seen since its 2003 premiere, with a performance by Coldplay.

Depeche Mode have applied their Celebrity and cultural longevity to help promote and raise funds for several notable charity endeavours. They lent their support to high-profile charities such as MusiCares, Cancer Research UK and the Teenage Cancer Trust. The band has also supported the Small Steps Project, a humanitarian organisation based in the United Kingdom, aiming to assist economically disadvantaged children into education. Since 2010, Depeche Mode have partnered with Swiss watchmaker Hublot to support Charity: Water, aimed at the provision of clean drinking water in developing countries. In 2014, the partnership hosted a gala and fundraiser at the TsUM building in Moscow, raising $1.4 million for the charity.

On 6 June 2011, as the final commitment to their contract with EMI, the band released a remix compilation album, entitled Remixes 2: 81–11 that features remixes by former members Vince Clarke and Alan Wilder. Other Remixers involved with the project were Nick Rhodes of Duran Duran, Röyksopp, Karlsson & Winnberg of Miike Snow, Eric Prydz, Clark and more. A new remix of "Personal Jesus" by Stargate, entitled "Personal Jesus 2011", was released as a single on 30 May 2011, in support of the compilation.

In October 2012 during a press conference in Paris, Dave Gahan, Martin Gore and Andy Fletcher announced plans for a new album and a 2013 worldwide tour starting from Tel Aviv and continuing in Europe and North America. Martin Gore revealed that Flood mixed the album, marking the producer's first studio collaboration with the band since 1993's Songs of Faith and Devotion.

That month, Depeche Mode won the award for "Best International Group – Rock / Pop" at the ECHO Awards in Germany. Also they were nominated at the category "Album des Jahres (national oder international)" for Delta Machine, but lost against Helene Fischer's Farbenspiel.

On 8 October 2014, the band announced Live in Berlin, the new video and audio release filmed and recorded at the O2 World in Berlin, Germany in November 2013 during the Delta Machine Tour. It was released on 17 November 2014 worldwide.

In September, the official Depeche Mode Facebook page hinted at a new release, later confirmed by the band to be a music video compilation, Video Singles Collection, scheduled for release in November by Sony. In October 2016, the band announced that their fourteenth album, titled Spirit and produced by James Ford, would be released in spring 2017. The group has also been nominated for the 2018 Rock and Roll Hall of Fame.

"Where's the Revolution," the lead single from Spirit, was released 3 February 2017, along with its lyric video. The official video was published a week later, on 9 February. The Global Spirit Tour officially kicked off on 5 May 2017 with a performance in Stockholm, Sweden, at the Friends Arena. The first leg of the tour covered European countries only, ending with a final stadium show in Cluj-Napoca, Romania, at the Cluj Arena. The second leg of the tour will cover North America and then return to Europe. The North America leg of the tour kicked off in Salt Lake City, Utah, on 23 August, at the USANA Amphitheatre. The band will remain in North America until 15 November when they leave for Dublin and resume the European leg. The band will end the tour in South America with a final show on 27 March 2018 in São Paulo, Brazil, at the Allianz Parque.

Depeche Mode were nominated for induction into the Rock and Roll Hall of Fame in 2018.