Pakistani cricket fans show their tickets at the National stadium in Karachi on Friday. AP
An unusual spell of monsoon rain in the southern port city during this time of the year left the cricket ground completely waterlogged.
Umpires called off the match at 4:30pm local time with no chance of any play.
The second game of the three-match series, which could also be affected by rain, is on Sunday.
Only a few hundred spectators braved the rain and made it to the stadium.
"We came here to watch the match as Sri Lanka has come here after 10 years, we were excited," said cricket fan Anam Salman at the National Stadium. "We walked a long way in rainy weather but after coming here we are very disappointed ... What can we do? We can just hope for the best for the rest of the two matches."
Karachi hasn't hosted an ODI in 10 years since Sri Lanka last played here in 2009.
It is the first time since Sri Lanka's team bus was attacked in Lahore in 2009 that a foreign team will conduct a two-week tour of Pakistan with Karachi hosting all three ODIs. Major teams have avoided Pakistan since that ambush, which killed eight people and injured several players.
Another fan appreciated Sri Lanka sending its team to Pakistan, despite 10 Sri Lanka players pulling out of the limited-overs series due to security reasons.
"We must appreciate Sri Lanka Cricket for sending their team after 10 years, we hoped to enjoy some good cricket, but it's disappointing that we didn't have a match because of rain," Azeem Rahat said.
The ODI series will be followed by three Twenty20s at Lahore.
"History will be made on Friday when Karachi will host the first ODI," said Pakistan captain Sarfaraz Ahmed. "We must thank the Sri Lankan team for touring us."
Pakistan rode on a brilliant century from Babar Azam and fast bowler Usman Shinwari’s five wickets to beat Sri Lanka by 67 runs in the second day-night international on Monday
The 28-year-old left-hander knocked a 134-ball 133 with 16 boundaries and a six for his second hundred which lifted Sri Lanka after they won the toss and batted on a flat National stadium pitch.
India skipper Virat Kohli said on Sunday the team’s “hunger” to keep improving has led to their record 11th-straight Test series win at home after outplaying South Africa by an innings and 137 runs.
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