Mycotoxin contamination of foodstuffs is a serious food safety concern globally as the prolonged ingestion of these toxins has the tendency to worsen the risk of hepatocellular carcinoma. This study aimed at estimating ochratoxin A (OTA) and aflatoxin (AF) levels above international (European Food Safety Authority, EFSA) and local (Ghana Standards Authority, GSA) standards as well as the health risks associated with the consumption of maize (n = 180) sampled from six (6) regions representing the agro-ecological zones of Ghana. OTA and AF were measured with High-Performance Liquid Chromatography with a Fluorescence detector. Out of the 180 samples analyzed for total aflatoxins (AFtotal), 131/180 tested positive and 127 (70.50%) exceeded the limits of EFSA and ranged 4.27–441.02 µg/kg. While for GSA, 116 (64.44%) of samples exceeded this limit and ranged between 10.18 and 441.02 µg/kg. For OTA, 103/180 tested positive and 94 (52.22%) of samples between the range 4.00–97.51 µg/kg exceeded the tolerable limit of EFSA, whereas 89 (49.44%) and were in the range of 3.30–97.51 µg/kg exceeded the limits of GSA. Risk assessment values for total aflatoxins (AFtotal) ranged between 50 and 1150 ng/kg bw/day, 0.4–6.67, 0–0.0323 aflatoxins ng/kg bw/day and 1.62–37.15 cases/100,000 person/year for Estimated Daily Intake (EDI), Margin of Exposure (MOE), Average Potency, and Cancer Risks respectively. Likewise, ochratoxin (OTA) values were in the ranges of 8.6 × 10–3–450 ng/kg bw/day, 0.05–2059.97, 0–0.0323 ochratoxins ng/kg bw/day and 2.78 × 10–4–14.54 cases/100,000 person/year. Consumption of maize posed adverse health effects in all age categories of the locations studied since the calculated MOE values were less than 10,000.