Shama Sikander Gesawat was born in Makrana, Rajasthan, India, and is the daughter of Gulshan, a housewife and Sikander Gesawat who was a marble supplier and now practices ayurveda. At the age of 10 her family moved to Mumbai, Maharashtra, where she lived together with her younger siblings, Khalid, Rizwan, and Salma (born 1991). Sikander has mentioned in interviews that her early years in Mumbai were extremely difficult, even commenting that at times "there was no food in the house to feed the family".

Having moved locations frequently, Sikander attended as many as nine schools in her early life in Makrana and in various parts of Greater Mumbai including Malad, Mumbra, Thane, and Andheri. Following her completion of the 10th grade, and passing the Indian Certificate of Secondary Education examination, Sikander enrolled in the Roshan Taneja School of Acting in Mumbai in 1995, graduating from the course a year later.

Her film debut came at the age of 16, in 1998 with the Hindi-language feature film Prem Aggan produced and directed by acclaimed film personality Feroz Khan. After a friend suggested she screen test for the part, Sikander so impressed Feroz Khan that she landed the role, even though it had already been cast. Despite significant hype, the film, which also featured Feroz Khan's son Fardeen Khan's debut, was both a critical and box office failure. Nevertheless, one critic praised her screen presence and commented "[Sikander is] friendly to the viewers' eyes."

A year later Sikander appeared in the Amir Khan starer Mann (1999 Hindi) in a cameo as Kamini. Directed by Indra Kumar the film received mixed reviews and did not do well at the box office. As with her debut in Prem Aggan, however, Sikander received positive reviews for her performance. Calling her "pretty and emotive", Mohammad Ali Ikram of Planet Bollywood exclaimed "Mark my words, this simple stunner has the ability to shine as a great performer and star".

Ansh: The Deadly Part (2002) was Sikander's first supporting role in a Hindi language feature film. Portraying the character Kusum opposite south Indian actor Abbas, the film produced by Rukamanee Arts was a box office success doing reasonably well and garnering generally favorable reviews. Despite Ansh being her best-faring feature film so far, Sikander would not have another big screen release for the next six years.

Though her feature films failed to establish Sikander as a box office success, her Television debut portraying the title character 'Pooja Metha' in the popular Sony TV drama Ye Meri Life Hai (2003-2005) made the show a household name overnight, gave her "instant fame", and eventually elevated her to "one of the most loved faces on Indian television.". Her performance earned her numerous nominations, her wins including The Indian Television Academy Awards' "GR8 Face of the Year" (2004), The Indian Television Academy Awards' "Best Debut" (2004), The 12th Annual Lion's Gold Awards' "Best Actress: Critics' Choice" (2005), and Sony TV's "Best Face" (2005).

Fueled by the success of Ye Meri Life Hai and her subsequent performances, Sikander would be seen in frequent guest appearances on various popular programs including Batliwala House No. 43 (in 2005), C.I.D. (Indian TV series) (in 2006), Jodee Kamaal Ki (in 2007), Kaajjal (in 2008), and Man Mein Hai Visshwas (in 2009).

She has been featured in numerous magazine spreads as well as appearing on the cover of GR8! Magazine more than any other Actress, three times for the English Edition: March 2010, July 2006, February 2005, as well as at least twice for the Hindi Edition. She also appeared on the cover of Showtime Magazine in December 2011. Sikander was deemed October 2011's 'Hottie of the Month' by Perfect Woman Magazine, and featured in the 'Perfect Woman Spotlight' in May 2013 and Zing Magazine's 'Travel Diaries' in March 2013.

Beginning in 2007 Sikander also featured as a TV program Host – first of entertainment channel Zoom's Popkorn Newz for a single season, and then in 2008, as the host of the STAR One travel-contest program Jet Set Go. An accomplished self-taught Dancer and amateur singer, 2008 would also see Sikander appear on numerous programs including Celebrity dance program Ek Khiladi Ek Haseena as a Celebrity contestant alongside notable Indian cricketer Vinod Kambli (where she drew praise from Bollywood Superstar Sushmita Sen who called her "one of the most fabulous Dancers I've ever seen"), next in the singing reality program Jjhoom India again as a Celebrity contestant, as well as India's longest running dance program Boogie Woogie as a Celebrity guest performer in 2010 and subsequently on multiple occasions as a performer as a guest judge. Her ability to showcase well in singing, dance, hosting as well as acting caused critics to comment on her versatility as a performer, identifying her as one of the few who have been able to navigate between film and television. While her TV career flourished, Sikander returned to film in 2008 with a supporting role in Director Shashi Ranjan's Dhoom Dhadaka alongside notable Bollywood actors Jackie Shroff, Anupam Kher, Gulshan Grover, and Satish Kaushik. The film was a box office failure and regarded by critics as average to disappointing. Sify's Sonia Chopra commented that "The cast doesn't disappoint as much as the film", and that "Shama Sikander [is] earnest enough ... molten-hot and ... superbly styled".

In 2010 Indian gossip columnist Vicky Lalwani linked Sikander to actor Mimoh Chakraborty – a claim both parties denied.

In mid-2011 speculation began regarding Sikander's relationship with India-based American actor / musician Alexx O'Nell The two were spotted with increasing frequency throughout 2011 and Sikander confirmed that they were indeed in a relationship in an interview which featured on the cover of Showtime Magazine's December 2011 issue, entitled "Shama Sikander Finally Breaks Her Silence on Her Relationship With Alexx O'Nell". Later, a June 2012 interview with Sikander disclosed that the two met through friends at a sundown party .. and that she was "won over nearly immediately after he played some music for her ... [O'Nell's original] compositions ... to be featured in an album that will release soon." Sikander and O'Nell's relationship was confirmed to be over in January 2015.

Having previously featured in a number of music videos in Punjabi and other Indian languages (most notably for acclaimed singer Abhijeet) in late 2012 Sikander reportedly produced a (very sensuous) music video featuring herself alongside boyfriend actor / musician Alexx O'Nell picturising his original English language composition entitled 'Still on My Mind'. The video, which marks their first on screen collaboration has not yet been released, and it is uncertain if it was produced under the newly formed Chocolate Box Films Pvt. Ltd. banner. Reports also indicate that she may be producing an entire English language album authored by O'Nell.

In January 2016, it was confirmed that Sikander got engaged to American businessman James Milliron in Dubai, UAE.