Describing diet-related effects on the gut microbiome is essential for understanding its interactions with fat and/or sugar-rich diets to promote obesity-related metabolic diseases. Here, we sequenced the V3-V4 hypervariable region of the bacterial 16S rRNA gene to study the composition and dynamics of the gut microbiome of adult mice fed diets rich in fat and/or sugar, at 9 and 18 weeks of diet. Under high-fat, high-sugar diet, the abundances ofTuzzerellaandAnaerovoraxwere transiently increased at 9 weeks, whileLactobacillusremained elevated at 9 and 18 weeks. The same diet decreased the abundances ofAkkermansia,Paludicola,Eisenbergiella, andButyricicoccusat 9 and 18 weeks, whileIntestinimonasand UCG-009 of theButyricicoccaceaefamily responded only at 18 weeks. The high-fat diet decreased the abundances of UBA1819 at 9 weeks, andGastranaerophilales,ClostridiaUCG-014, and ASF356 at 9 and 18 weeks. Those ofMarvinbryantia,Harryflintia,Alistipes,Blautia,LachnospiraceaeA2, Eubacterium coprostanoligenes group, and Eubacterium brachy group were lowered only at 18 weeks. Interestingly, these genera were not sensitive to the high-sugar diet. The mouse gut microbiome was differentially affected by diets rich in fat or fat and sugar. The differences observed at 9 and 18 weeks indicate a progressive microbiome response.