Mouse models are increasingly employed in the comprehension of cardiovascular disease. Wave Intensity Analysis (WIA) can provide information about the interaction between the vascular and the cardiac system. We investigate age-associated changes in WIA-derived parameters in mice and correlate them with biomarkers of cardiac function. Sixteen wild-type male mice were imaged with high-resolution ultrasound (US) at 8 weeks (T ₀) and 25 weeks (T ₁) of age. Carotid pulse wave velocity (PWV) was calculated from US images using the diameter–velocity loop and employed to evaluate WIA. Amplitudes of the first (W ₁) and the second (W ₂) local maxima, local minimum (W _b) and the reflection index (RI = W _b/W ₁) were assessed. Cardiac output (CO), ejection fraction (EF), fractional shortening (FS) and stroke volume (SV) were evaluated; longitudinal, radial and circumferential strain and strain rate values (LS, LSR, RS, RSR, CS, CSR) were obtained through strain analysis. W ₁ (T ₀: 4.42e-07 ± 2.32e-07 m²/s; T ₁: 2.21e-07 ± 9.77 m²/s), W ₂ (T ₀: 2.45e-08 ± 9.63e-09 m²/s; T ₁: 1.78e-08 ± 7.82 m²/s), W _b (T ₀: −8.75e-08 ± 5.45e-08 m²/s; T ₁: −4.28e-08 ± 2.22e-08 m²/s), CO (T ₀: 19.27 ± 4.33 ml/min; T ₁: 16.71 ± 2.88 ml/min), LS (T ₀: 17.55 ± 3.67%; T ₁: 15.05 ± 2.89%), LSR (T ₀: 6.02 ± 1.39 s⁻¹; T ₁: 5.02 ± 1.25 s⁻¹), CS (T ₀: 27.5 ± 5.18%; T ₁: 22.66 ± 3.09%) and CSR (T ₀: 10.03 ± 2.55 s⁻¹; T ₁: 7.50 ± 1.84 s⁻¹) significantly reduced with age. W ₁ was significantly correlated with CO (R = 0.58), EF (R = 0.72), LS (R = 0.65), LSR (R = 0.89), CS (R = 0.61), CSR (R = 0.70) at T ₀; correlations were lost at T ₁. The decrease in W ₁ and W ₂ suggests a cardiac performance reduction, while that in W_b, considering unchanged RI, might indicate a wave energy decrease. The loss of correlation between WIA-derived and cardiac parameters might reflect an alteration in cardiovascular interaction.