Higuain, signed after leaving Serie A champions Juventus, missed a penalty as his side suffered a 3-0 loss at Subaru Park.
The former Real Madrid forward almost made a dream start to his career in the United States, hitting the outside of the post with a bicycle kick in the 20th minute.
With his team trailing 2-0, Higuain had a chance to get Inter Miami back into the game in the 77th minute, but he blazed a penalty over the crossbar and reacted angrily after Union players celebrated his miss.
Higuain has now failed to score with his past four penalty attempts in all competitions.
Anthony Fontana, Ilsinho and Brenden Aaronson were on the scoresheet for Philadelphia as struggling Inter Miami were left in second bottom in the Eastern Conference.
Despite Higuain’s disappointing start at Miami, coach Diego Alonso has previously stressed his arrival can benefit the club in a number of ways.
“The arrival of experience has a positive impact on the team, first because of the quality because it helps improve the level and also it impacts the young players and helps them to develop,” Alonso told AFP earlier this month.
“It is a double benefit. We have seen it with Matuidi and if we are able to finish the signing of Gonzalo, they will both be able to benefit us in these ways.”
Upon sealing his move to MLS, Higuain declared his desire to embrace a new experience and help Miami achieve early success.
“First of all, I want to thank Inter Miami for the effort it has made to sign me,” Higuain said. “I think it will be a beautiful experience in my life. It’s what I was looking for — a new experience, a new league and a beautiful city.
“I feel good, I feel whole as a player. I’m motivated to try a new league and help the team grow. Individually, my goal is to demonstrate that I can contribute and continue playing great football here, and I hope I can achieve that because I have all the tools necessary to succeed.
“Inter Miami is a team in construction, but there is already a good base to reach important goals.”