In 1998, Lacey along with Garrett Tierney, Brian Lane and Brandon Reilly formed The Rookie Lot, who would self-release a split EP as well as a demo tape.

In November 1999, Lacey formed Taking Back Sunday with Guitarist Eddie Reyes; after adding Nolan to the band, Lacey moved to bass guitar. He contributed bass guitar and backing vocals to their first EP in 2001, but left the band during the recording sessions after Nolan slept with Lacey's girlfriend.

This would lead Lacey to write "Seventy Times 7", which appeared on Brand New's 2001 album Your Favorite Weapon, while Nolan would later write about the dispute from his perspective in the Taking Back Sunday track "There's No I in Team". Later, Lacey and his Brand New bandmates stated that the "situation cleaned itself up a lot sooner than most people thought it did", and that the situation had been blown out of proportion by fans and the media. Lacey has described fellow musician Kevin Devine as one of his best friends, as well as citing him as a musical influence.

Early on in his career as a musician Lacey cited bands such as Lifetime, Foo Fighters, The Cars and Pearl Jam as influences for himself and Brand New. He later taped the words "Hi Moz", a reference to The Smiths frontman Morrissey, to his guitar during their performance of "The Quiet Things That No One Ever Knows" on Jimmy Kimmel Live! in 2003.

One of Lacey's first solo shows was on April 27, 2004 at The Downtown in Farmingdale, New York, performing a mixture of covers and songs by his band, Brand New. In July 2007, Lacey and Devine would tour in the United States, with Lacey once again performing material from Brand New, as well as performing various tracks with Devine.

Outside of Brand New, Lacey has frequently collaborated with Kevin Devine, both in the studio and live. In 2005, Lacey was featured Kevin Devine's album Split the Country, Split the Street, providing vocals on the songs "Cotton Crush", "Afterparty", and "No One Else's Problem". In 2009, he would again contribute to the album Brother's Blood, singing on "Tomorrow's Just Too Late".

During the writing and recording of the 2006 album The Devil and God Are Raging Inside Me, Lacey was particularly influenced by bands such as U2 and Radiohead to try writing using instruments other than the guitar.

Other appearances by Lacey include contributing bass guitar to the track "Rocket" on the Intramural 2007 album This Is a Landslide, as well as providing bass and guitar on Grace Read's song "Cloak and Dagger", from her EP Young Guns.

In 2008 he once again toured with Devine, and in an interview discussed how at this point he wished only to occasionally tour and perform Brand New material solo, believing that "the songs lack meaning" without his band beside him.

In 2013, Lacey produced the album Bubblegum. Lacey was initially nervous, as it was the first album he had produced outside of Brand New. Along with Kevin Devine, Lacey frequently appeared onstage and on tour with Manchester Orchestra.

At various Brand New shows in 2014 and 2015, Lacey joined support band Dinosaur Pile-Up on stage, performing their track "Nature Nurture".

In 2015, Lacey, along with Mike Sapone, co-produced the track "Aerobed" for the band Cymbals Eat Guitars, as part of the Devinyl Splits series, curated by Kevin Devine.

In late 2017, Lacey was accused of sexual misconduct by two women in the 2000s, including soliciting naked photographs from underage fans. Lacey apologized publicly on Brand New's Facebook page and admitted to having a sex addiction throughout the band's early career, having since had counseling and treatment without it being public knowledge until the allegations surfaced.