Nani was ruled out of the tournament earlier in the day due to a shoulder injury which he sustained in training in Portugal after falling while attempting an acrobatic shot.
"In my 30-year career in sports this was the most difficult case I had to deal with, but he was in pain and there was no other option," coach Carlos Queiroz told reporters.
Possibly as a result, Queiroz chose the safe option against Mozambique and started Cristiano Ronaldo on the bench.
The 28,000-strong crowd at the Wanderers cricket ground were disappointed not to see the world's most expensive player start and made the stands shake when he finally came on in the 62nd minute.
Danny was the liveliest Portuguese player from the start, linking up well with Deco and Simao as Portugal missed a host of chances.
It was the African team, however, who came closest to scoring, when midfielder Hagy fired a thunderous long distance shot that crashed against Eduardo's post on 40 minutes.
The Portuguese took control in the second half, with Danny sidestepping keeper Lama after a Deco through ball to score on 52 minutes. The Zenit player turned provider in the 75th minute, making a fine assist for substitute Hugo Almeida to tap in.
"I started today and things went well. But we are all very sad for Nani. In my opinion he was the player in the best form from all of us," Danny said.
Portugal also had positive news on injuries, with midfielder Pepe coming on for the last quarter of hour to play for the first time since sustaining a knee injury in December.
"I was quite anxious before the match, it was as if I was going to play the first match in my life...while we were warming up, Ronaldo told me to remain calm, which helped," he said.
Ronaldo's main contribution to the match came in the 83rd minute, when his powerful drive was parried by Lama straight to Almeida who scored his second with another simple finish.
Portugal begin their World Cup Group G campaign against Ivory Coast on June 15 before matches with North Korea and Brazil.
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