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Leicester's Selby, who beat Ding Junhui in last year's final, looked on course for a whitewash by going 8-0 ahead.
Irishman O'Brien claimed the ninth and 11th to avoid becoming only the second player to exit without winning a frame, but Selby wrapped up the match.
He will face either Wales' Ryan Day or China's Xiao Guodong in the next round.
Selby has enjoyed a stellar season - claiming four ranking titles, including this month's China Open, though no player has followed that by winning the world title in the same season.
The world number one made top breaks of 92, 77 and 66 as he began his attempt to win his third title at the Sheffield venue, which is holding the event for a 40th year.
"I'm very happy to get through and happy with the scoreline but my performance could have been better," Selby said. "I was not killing enough frames off in the first visit and would have liked to have capitalised on them.
"I would like to win every tournament I play in. I am confident and I am playing well enough.
"Even if I don't play well, I have a never-say-die attitude and you have to scrape me off the table.
"I was gutted not to go 9-0 because I know the history that there has only been one whitewash here. I was devastated to go in after the first session at 8-1."
Having made light work of O'Brien, Selby has almost a week off, returning to action next Saturday.
Dubliner O'Brien came through qualifying by beating David Gilbert in a final-frame decider - the longest frame in snooker history, timed at two hours, three minutes and 41 seconds.
But he struggled badly in the first-round encounter, managing a high break of just 32, although he avoided the ignominy of joining Eddie Charlton - who lost 10-0 to John Parrott in 1992 - as the only players not to win a frame at the championship.
He has now lost six successive meetings against Selby, claiming just four frames in a run stretching back to 2006.
"When I won my first frame, it was good because the crowd were so supportive and willing me not to get the whitewash," said O'Brien.
In an all-Scottish tie, qualifier Stephen Maguire claimed eight frames in a row to trounce Anthony McGill 10-2.
Maguire, who has won five ranking titles, has fallen to 24th in the world but was in good scoring form, compiling breaks of 97, 66 and 60 to go through.
Meanwhile, five-time champion Ronnie O'Sullivan was pegged back to a 5-4 lead over debutant Gary Wilson.
Former taxi driver Wilson fell 5-1 behind but took the last three frames of the session, including the ninth having needed snookers.
On the other table, Kyren Wilson leads 5-4 against Crucible first-timer David Grace.
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Defending champion Mark Selby reached the second round of the World Championship by thrashing Fergal O'Brien 10-2 at the Crucible Theatre.