Delaney was raised in Marblehead, Massachusetts. He attended New York University’s Tisch School of the Arts and graduated with a degree in musical theater in 1999.

Delaney has publicly shared his experience with depression and alcoholism. In 2002, Delaney blacked out while driving and drove his car into a building owned by the Los Angeles Department of Water and Power. In the wreck, he broke his left wrist and right arm, and had both of his knees scratched to the bone. This prompted Delaney to stop drinking.

Delaney first came to the attention of the public via Twitter, on which he started posting in 2009. By 2016, Delaney had over 1.2 million followers. While other comics were hesitant to share their material on social media, Delaney is considered one of the first comedians to use social media to publish jokes. Delaney credits comedy writer and director Graham Linehan with his rise in popularity after Linehan began responding to Delaney’s tweets.

In 2010, Paste magazine named Delaney one of the ten funniest people on Twitter. In May 2012, he became the first comedian to win the ‘Funniest Person on Twitter Award’ at The Comedy Awards hosted by Comedy Central.

In December 2011, Comedy Central announced that Delaney would shoot a pilot for a variety show, called @RobDelaney. However, the series was not picked up.

His book Rob Delaney: Mother. Wife. Sister. Human. Warrior. Falcon. Yardstick. Turban. Cabbage. was published by Spiegel & Grau in November 2013.

Since moving to the UK in 2014, Delaney has appeared on several British panel shows, including Have I Got News for You, Would I Lie to You?, 8 Out of 10 Cats Does Countdown, The Big Fat Quiz of the Year and Room 101. In 2016, he appeared on Travel Man as a guest host for Seville, Spain.

Instead, Delaney moved on to co-write and co-star with Sharon Horgan in Catastrophe, that began airing in the UK on January 19, 2015 on Channel 4. The show follows their characters after they get together following a brief affair while he is in the UK on business, and then moves there permanently after he learns that she has become pregnant. It debuted in the United States on Amazon in June 2015. There are now four seasons available with the fourth season confirmed to be the final of the series. Channel 4 aired the concluding episode on February 12, 2019, while Amazon announced the US release date to be March 15 of the same year. The series earned him his sole Emmy nomination, for “Outstanding Comedy Writing”.

Delaney is a democratic socialist and often writes about political issues. He has said that he chooses presidential candidates based mostly on their policies regarding education and health care, reasoning: “Make it easier for your citizens to be healthy and smart and they will save you in ways you have yet to imagine.” He supported Bernie Sanders in the 2016 Democratic primary and voted for Hillary Clinton in the subsequent general election. After Donald Trump was elected president, Delaney joined the Democratic Socialists of America, the National Association for the Advancement of Colored People, and the American Civil Liberties Union. In February 2019, Delaney endorsed Senator Bernie Sanders in his second presidential campaign.

In 2016, Delaney’s reaction to the UK’s vote to leave the EU was “Wow people are idiots” and he later referred to the Brexit Party as an “army of morons and bigots”. In June 2017, despite being ineligible to vote as a non-UK citizen, Delaney endorsed the Labour Party in the 2017 UK general election. In November 2018, he supported a petition organised by Labour campaign group Momentum calling on Labour MPs to vote against the EU withdrawal agreement which had been negotiated by Theresa May’s government.

Delaney is an Irish American. Delaney is married; he and his wife, Leah Delaney, have four sons, one of whom died in January 2018. In February 2018, Delaney publicly shared that their son Henry had died, age two and a half, the month before, after having been diagnosed with a brain tumor in 2016 and receiving extensive treatment. The couple’s fourth son was born in August 2018. Delaney and his family live in London.

Throughout 2019, Delaney ventured in a series of cameos in feature films. He reteamed with director David Leitch and performer Ryan Reynolds for Hobbs & Shaw, in which he appeared as Agent Loeb. He appeared as a theater director in Paul Feig’s comedy-drama Last Christmas in a brief scene with Peter Serafinowicz, Sara Powell and Emilia Clarke. Both movies were #1 at the UK box office. He also appeared opposite Anne Hathaway in The Hustle as Todd and the Fox News drama Bombshell co-starring Charlize Theron. He filmed a cameo as Elvis Presley in Dexter Fletcher’s Elton John musical biopic Rocketman, which was omitted from the theatrical cut. It was also reported that he would appear opposite Reynolds another time, in Pokémon: Detective Pikachu. However, he did not appear in the final film. In September 2019 he was cast in The Good House opposite Sigourney Weaver and Kevin Kline.

In November 2019, along with other public figures, he signed a letter supporting Labour Party leader Jeremy Corbyn describing him as “a beacon of hope in the struggle against emergent far-right nationalism, xenophobia and racism in much of the democratic world” and endorsed him in the 2019 UK general election. In December 2019, along with 42 other cultural figures, he signed a letter endorsing the Labour Party under Corbyn’s leadership in the 2019 general election. The letter stated that “Labour’s election manifesto under Jeremy Corbyn’s leadership offers a transformative plan that prioritises the needs of people and the planet over private profit and the vested interests of a few.”

Delaney wrote about his experience of getting a vasectomy in 2020.