<p>This study investigated mathematics teachers’ awareness, perceptions, and challenges in using ChatGPT for mathematics instruction within the Ghanaian context. Although research on artificial intelligence (AI) in education is expanding, few empirical studies have examined Ghanaian mathematics teachers’ awareness and experiences with ChatGPT, creating a critical gap in the literature. A census sampling approach was employed, involving all 50 mathematics teachers at Adu Gyamfi Senior High School in the Sekyere South District of Ghana. Data were collected using a structured questionnaire that underwent content and face validity checks by experts and achieved acceptable reliability, with Cronbach’s alpha values ranging from 0.78 to 0.87 across the constructs of awareness, perceptions, and challenges. Descriptive statistics generated through SPSS revealed considerable awareness (<i>M</i> = 3.74–3.95) and generally favorable perceptions of ChatGPT’s usefulness and ease of use (<i>M</i> = 3.86–4.14). However, substantial challenges were also identified, including time constraints, inadequate training, poor internet connectivity, limited access to digital devices, and insufficient institutional support (<i>M</i> = 3.82–4.00). The findings suggest that while teachers demonstrate openness to adopting ChatGPT, systemic barriers hinder its effective integration into classroom practice. The study highlights the need for targeted professional development, infrastructure improvement, and supportive policies to enable the sustainable adoption of AI tools in mathematics education within resource-constrained contexts.</p>