Paul Stirling was unable to bat for Ireland after sustaining an injury to his finger while fielding during their own innings.
Namibia posted 316-7 in 50 overs, with Jan Frylinck scoring 126 and captain Gerhard Erasmus adding 54.
Louren Steenkamp opened the batting for the visitors before being dismissed for 13 runs after winning the toss to bat first.
Alex Volschenk contributed 36 runs to help Namibia reach their target in the allotted time.
Ireland batted second, reaching 56-4 before Curtis Campher struck a century on 86 balls to provide hope for victory.
Bernard Scholtz, Ruben Trumpelmann and Jack Brassell each claimed two wickets during Ireland's innings.
Despite the breakthrough from the Irish bowlers, wickets continued to fall regularly as the side reached their total of 253 all out in 44.5 overs.
The match ended with Namibia winning by 63 runs, leaving Ireland trailing 2-1 in a five-match One Day International series.
The sides are scheduled to play two further encounters on Friday and Sunday ahead of next year's World Cup qualifiers.
Stirling remains the skipper for both teams despite his absence from the batting lineup.
Curtis Campher was the standout performer for Ireland, taking two wickets himself in response.
Jan Frylinck and Malan Kruger were also notable contributors for Namibia with 42 runs respectively.
The victory marks a significant step forward for the visitors in their campaign against the hosts.
Ireland will now focus on recovering from the setback before their next scheduled fixtures.
No further details regarding Stirling's injury timeline have been released at this stage.