Proposed mechanisms for the production of calcium in the first stars (population III stars)—primordial stars that formed out of the matter of the Big Bang—are at odds with observations. Advanced nuclear burning and supernovae were thought to be the dominant source of the calcium production seen in all stars. Here we suggest a qualitatively different path to calcium production through breakout from the ‘warm’ carbon–nitrogen–oxygen (CNO) cycle through a direct experimental measurement of the ¹⁹F(p, γ)²⁰Ne breakout reaction down to a very low energy point of 186 kiloelectronvolts, reporting a key resonance at 225 kiloelectronvolts. In the domain of astrophysical interest, at around 0.1 gigakelvin, this thermonuclear ¹⁹F(p, γ)²⁰Ne rate is up to a factor of 7.4 larger than the previous recommended rate. Our stellar models show a stronger breakout during stellar hydrogen burning than previously thought^,,, and may reveal the nature of calcium production in population III stars imprinted on the oldest known ultra-iron-poor star, SMSS0313-6708. Our experimental result was obtained in the China JinPing Underground Laboratory, which offers an environment with an extremely low cosmic-ray-induced background. Our rate showcases the effect that faint population III star supernovae can have on the nucleosynthesis observed in the oldest known stars and first galaxies, which are key mission targets of the James Webb Space Telescope.