Pinsky was born in Pasadena, California. His father, Morton Pinsky (1925–2009), was a physician whose parents emigrated from Ukraine. His mother, Helene Stanton (née Eleanor Mae Stansbury; 1925-2017), was a singer and Actress who came from a "highly Victorian upper-middle-class family in Philadelphia". Pinsky attended Polytechnic School. He majored in biology at Amherst College, graduating in 1980, and earned his M.D. at the University of Southern California School of Medicine in 1984. He served his residency in internal Medicine at USC County Hospital and became chief resident at Huntington Memorial Hospital in Pasadena, and eventually moved into private practice.

Pinsky's first television appearance was as a contestant on Wheel of Fortune in 1984, though he did not win. He also served as "health and human relations expert" on the first season of the U.S. TV series Big Brother in 2000.

Pinsky married on July 21, 1991, and he and his wife, Susan Sailer, had triplets Douglas, Jordan, and Paulina in November 1992.

In 1999, Pinsky co-founded an Internet-based community and advice site for teenagers called DrDrew.com with Curtis Giesen. Among their early backers was Garage.com. DrDrew.com soon ran out of funding, and the company was sold to Sherwood Partners Inc., a corporate restructuring firm, which sold the remnants to DrKoop.com in November 2000. Pinsky re-acquired the site circa 2013 and began using for general information about his books, radio and TV shows, as well as hosting his independent podcast, The Dr. Drew Podcast. In September 2012, Pinsky announced on The Adam Carolla Show that he will be doing a podcast on the Carolla Digital network.

In 2003, Pinsky authored Cracked: Putting Broken Lives Together Again, recounting his experiences as the Medical Director of the Department of Chemical Dependency Services at the Las Encinas Hospital drug rehabilitation clinic in Pasadena, California. He also contributed to the book When Painkillers Become Dangerous: What Everyone Needs to Know About OxyContin and Other Prescription Drugs, published in 2004.

On November 27, 2007, Pinsky began Dr. Drew Live, another nationally syndicated talk radio show where he focused on a wider range of health issues. It originated from KGIL in Los Angeles, originally airing weekdays from 11:00 am to 1:00 pm PT The show was canceled in December 2008.

Pinsky was honored with the Larry Stewart Leadership and Inspiration Award at the 12th Annual PRISM Awards in 2008.

Pinsky's father, Morton, died suddenly of a cerebral hemorrhage on October 27, 2009. A title card at the end of the season 3 finale of Celebrity Rehab dedicated the episode to him. Pinsky's mother, Helene, died on June 7, 2017 at age 91.

In September 2013, Pinsky revealed that he had recovered from prostate cancer surgery performed earlier that June and July, after which Pinsky did not require chemotherapy or radiation.

Pinsky also narrated for the 2014 documentary "Divorce Corp."

On January 5, 2015, Pinsky launched a new weekday program, "Dr. Drew Midday Live with Mike Catherwood," on KABC in Los Angeles.

In early 2011, Pinsky began hosting his own show, Dr. Drew On Call on HLN that focuses on news involving health and addiction topics. On August 26, 2016, HLN and Pinsky announced that the show's last episode would be September 22 of that year.