Sewage sludge should primarily find use in agriculture, reducing the quantity directed towards alternative disposal methods like incineration or deposition in municipal landfills. This study evaluated the agronomic value and the risk of soil and plant tissue contamination with heavy metals in sewage sludge obtained from two wastewater treatment plants (WWTP). The experiment was arranged as a 2 × 5 factorial (two sewage sludges, five sanitation treatments), involving lettuce cultivation in pots over two growing cycles. The two sewage sludges were sourced from the WWTPs of Gelfa and Viana do Castelo and underwent five sanitation and stabilization treatments (40% and 20% calcium oxide, 40% and 20% calcium hydroxide, and untreated sewage sludge). The Gelfa sewage sludge, characterized by a higher initial nitrogen (N) concentration, resulted in greater dry-matter yield (DMY) (12.4 and 8.6 g plant−1 for the first and second growing cycles, respectively) compared to that from Viana do Castelo (11.0 and 8.1 g plant−1), with N release likely being a major factor influencing crop productivity. The high N concentration and the low carbon (C)/N ratio of sewage sludge led to rapid mineralization of the organic substrate, which additionally led to a higher release of other important nutrients, such as phosphorus (P) and boron (B), making them available for plant uptake. Alkalizing treatments further stimulated sewage sludge mineralization, increasing soil pH and exchangeable calcium (Ca), thereby enhancing Ca availability for plants, and indicating a preference for use in acidic soils. Cationic micronutrients were minimally affected by the sewage sludge and their treatments. The concentrations of heavy metals in the sewage sludge, soils, and lettuce tissues were all below internationally established threshold limits. This study highlighted the high fertilizing value of these sewage sludges, supplying N, P, and B to plants, while demonstrating a low risk of environmental contamination with heavy metals. Nevertheless, the safe use of sewage sludge by farmers depends on monitoring other risks, such as toxic organic compounds, which were not evaluated in this study.