Rennes, Mannarino was eliminated in the second round by Jurij Rodionov. At the Sofia Open, he was beaten in the first round by German qualifier Yannick Maden. Seeded fifth at the New York Open, he lost in the first round to eventual champion Reilly Opelka. Seeded eighth at the Delray Beach Open, he got his first win of the season by beating Brayden Schnur in the first round. He ended up losing in the quarterfinals to second seed John Isner. In Acapulco, he was defeated in the first round by third seed John Isner. At the Indian Wells Masters, he made it to the second round where he was eliminated by sixth seed Kei Nishikori; he served for the match at 6–5 in the third set but failed to close out the match. At the Miami Open, he was beaten in the second round by 13th seed Daniil Medvedev. Starting his clay-court season at the Monte-Carlo Masters, Mannarino lost in the first round to Cameron Norrie. Seeded second at the BNP Paribas Primrose Bordeaux, he reached the quarterfinals where he fell to ninth seed and eventual finalist, Mikael Ymer. In Madrid, he was defeated in the final round of qualifying by Martin Kližan. However, due to the withdrawal of Jo-Wilfried Tsonga, he was awarded a lucky loser spot into the main draw. He lost in the second round to eighth seed and eventual finalist, Stefanos Tsitsipas. As the top seed in Lisbon, he suffered a second round loss at the hands of Steve Darcis. Seeded sixth at the Geneva Open, he lost in the first round to Albert Ramos Viñolas. At the French Open, he was knocked out of the tournament in the second round by 14th seed Gaël Monfils. At the Rosmalen Grass Court Championships, his first grass-court tournament of the season, Mannarino reached the final by beating Dutch wildcard Thiemo de Bakker, fourth seed Fernando Verdasco, fifth seed David Goffin, and second seed Borna Ćorić. He defeated Jordan Thompson in the final to finally emerged victorious in an ATP Tour singles final after having lost all his previous six. Seeded second and two-time finalist at the Antalya Open, he reached the quarterfinals where he was beaten by eventual champion Lorenzo Sonego. At Wimbledon, he lost in the first round to 13th seed and 2017 finalist, Marin Čilić. Seeded second at the Hall of Fame Open, Mannarino was defeated