Previous UK studies investigating nontuberculous mycobacteria have been limited to reporting isolation from culture, not burden of disease. We assessed the burden of nontuberculous mycobacterial disease (NTMD) in UK primary care from 2006 to 2016. Using electronic healthcare records, we identified patients with NTMD using a strict definition including patients with guideline-directed treatment/monitoring. We described treatment regimens and incidence/prevalence in the general population and in patients with underlying chronic respiratory diseases. Incidence of primary care-managed NTMD in the general population decreased (2006 to 2016 rates per 100,000 person-years, 3.85 to 1.28). Average annual prevalence of NTMD in the general population was 6.38 per 100,000. Around 85% were taking antimycobacterial therapy; 53.2% were taking a guideline-recommended regimen. Incidence of NTMD in patients with respiratory disease decreased (2006 to 2016 rates per 100,000 person-years, 12.5 to 7.40). Average annual prevalence of NTMD in patients with respiratory disease was 27.7 per 100,000. This is the first UK study using nationally representative data to investigate the burden of NTMD managed within primary care. Incidence and prevalence of managed NTMD within primary care is gradually declining. Increasing complexity in the management of NTMD may be driving a shift in care to secondary settings.