It is the second time the Swiss curator has topped ArtReview's annual Power 100 list, having also done so in 2009.
Polish curator Adam Szymczyk was placed second in the list, climbing from 14th place last year.
Art dealers Iwan and Manuela Wirth topped the list in 2015, but they have dropped to number three.
Oliver Basciano, Deputy Editor of ArtReview, told BBC News: "To put it simply Hans Ulrich Obrist is everywhere.
"His network spreads globally, connecting artists, thinkers, scientists, curators and more. Through this network he proliferates ideas.
"And ideas, as opposed to necessarily objects, for better or worse, are what makes contemporary art tick currently."
US art dealer David Zwirner dropped a place to number four this year.
Sir Nicholas Serota, who recently announced he would leave the Tate after 30 years to chair the Arts Council, held his number five position.
Frances Morris, the newly-appointed director of Tate Modern, took joint fifth place with him.
The ArtReview top 10 is:
The 16-member international jury placed Chinese artist Ai Weiwei 10th on the list - a drop of nine places from his position last year.
New entries further down the list included feminist theorist Donna Haraway at number 43, British artist Ed Atkins at 50 and Indian art group Raqs Media Collective at number 86.
The judging panel is made up of writers, artists, curators and critics, who base their rankings purely on an individual's influence in the previous 12 months.
The full list can be found on the ArtReview website.
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Hans Ulrich Obrist, artistic director of the Serpentine Galleries in London, has been named the most powerful figure in the art world.